Overall we will continue studes of persistent infection and of the evolution of standard RNA virus and of D1 particles during long term persistence. We will continue to derive molecular clones of standard VSV, D1 particles and mutated virus from persistent infection. These will be used to help characterize and to sequence the biologically interesting mutants recovered from persistently infected cells. We will continue to isolate viral nucleocapsids from persistently infected cells and analyze these to gain insights into events occuring within persistently infected cells of all kinds. We will particularly be interested in ratios of viral to D1 nucleocapside, rates of synthesis, evidence for cyclic synthesis etc. In various types of persistence. We will continue our studies of persistently infected cells in vivo in nude mice, with specific emphasis upon the role of NK cells and interferon in rejection. We will continue our collaboraion with Drs. Reid and Bloom and colleagues at Albert Einstein Medical Center for these studies. We will determine the extent to which standard virus in persistent VSV infections is able to continue mutating to escape interference by the newly generated D1 particles arising after many years of persistence. The mechanisms of this escape from D1 particle interference will be explored by cross-protection studies matching various D1 particles and virus mutants.